The Nervous System Orchestrates and Integrates Craniofacial Development: A Review

Abstract

Development of a head is a dazzlingly complex process: a number of distinct cellular sources including cranial ecto- and endoderm, mesoderm and neural crest contribute to facial and other structures. In the head, an extremely fine-tuned developmental coordination of CNS, peripheral neural components, sensory organs and a musculo-skeletal apparatus occurs, which provides protection and functional integration. The face can to a large extent be considered as an assembly of sensory systems encased and functionally fused with appendages represented by jaws. Here we review how the developing brain, neurogenic placodes and peripheral nerves influence the morphogenesis of surrounding tissues as a part of various general integrative processes in the head. The mechanisms of this impact, as we understand it now, span from the targeted release of the morphogens necessary for shaping to providing a niche for cellular sources required in later development. In this review we also discuss the most recent findings and ideas related to how peripheral nerves and nerve-associated cells contribute to craniofacial development, including teeth, during the post- neural crest period and potentially in regeneration.

Keywords: craniofacial; development; glia; nervous system; stem cell; tooth.

Figure 1

Neural crest cells migrate from dorsal neuroectoderm and organize the facial development in vertebrate embryos. Colors highlights regions of the developing and adult face that correspond to different neural crest populations along the posterior axis.

Figure 2

Forebrain and FEZ exchange signals to shape the facial compartment. Factors produced by the epithelium in the frontal face (FEZ) control the formation of future skeletal elements together with signals coming from the developing forebrain. Manipulation of FEZ leads to changes in the shape of Figure 5. Peripheral nerves host and transport neural crest-derived associated glial cells that give rise to a number of cell types in developing body. Left: examples and position of nerve-derived cell types. A significant number of melanocytes (purple circles on a scheme) in a head-neck region is produced from recruited Schwann cell precursors. Additionally, some mesenchymal progenitors in developing teeth (shown as red ellipses) are also recruited from the peripheral nerves. At the same time all parasympathetic neurons in the head are derived from nerve-associated cells. Right: the spectrum of currently confirmed nerve-derived cell types in the developing face (right panel).

Figure 3

Developing eye and sensory placode-derived structures influence the development of surrounding skeletal and other tissues in the head. Upper part (in blue): developing eye influences the formation of surrounding skeleton as evidenced in blind cavefish and observed in the development of a flatfish. Integration of an eye into orbit provides the specie-specific view angle and stands behind stereoscopic vision. Left (in purple): otic vesicle and sensory ear components induce and integrate surrounding cartilage and bone. Lower part (in green): olfactory epithelium development influences formation of surrounding skeletal parts.

Figure 4

Peripheral sensory nerves inject Shh into variety of structures in the head and tune the activity of stem cell compartments. For instance, nerve-derived Shh plays an important role in controlling stem cell niches in continuously growing incisor, hair follicle, touch dome, and limbal region of cornea in the eye.

Figure 5

Peripheral nerves host and transport neural crest-derived associated glial cells that give rise to a number of cell types in developing body. Left: examples and position of nerve-derived cell types. A significant number of melanocytes (purple circles on a scheme) in a head-neck region is produced from recruited Schwann cell precursors. Additionally, some mesenchymal progenitors in developing teeth (shown as red ellipses) are also recruited from the peripheral nerves. At the same time all parasympathetic neurons in the head are derived from nerve-associated cells. Right: the spectrum of currently confirmed nerve-derived cell types.